Association between body roundness index and prevalence of kidney stone in the U.S: a study based on the NHANES database.

OBJECTIVE: This study aimed to evaluate the potential association between the body roundness index (BRI) and kidney stone prevalence in adults in the United States. METHODS: A cohort of participants from the National Health and Nutrition Examination Survey (NHANES) database spanning 2007-2018 were gathered for analysis. Logistic regression analyses, subgroup assessments, and calculations were employed to examine the potential link between BRI and kidney stone prevalence. RESULTS: The study included 30,990 participants aged > 20 years, of which 2,891 declared a kidney stone history. After modulating all relevant confounding factors, each unit increase in the BRI was linked to a 65% increase in kidney stone prevalence (OR = 1.65, 95% CI: 1.47, 1.85). Sensitivity analyses conducted by categorizing the BRI into three groups revealed a 59% increase in kidney stone prevalence in the highest tertile BRI group compared to the lowest one (OR = 1.59, 95% CI: 1.42, 1.79). Furthermore, dose-response curves depicted a positive near-linear correlation between the BRI and the risk of kidney stone prevalence. CONCLUSION: These findings suggest a clinically noteworthy positive correlation between higher BRI values and kidney stone prevalence among the studied US adult population. However, it is essential to acknowledge that the observed relationship does not establish a causal link.

Molecular mechanism of Rhizoma Polygonati in the treatment of nephrolithiasis: network pharmacology analysis and in vivo experimental verification.

Rhizoma Polygonati (RP) is the dried rhizome of the liliaceous plant. It has anti-inflammatory and anti-apoptosis effects. But its role in kidney stones has not been studied. The purpose of this study was to verify the effect of RP in the treatment of nephrolithiasis through network pharmacological analysis and in vivo experiments. The active compounds and protein targets of RP, as well as the potential targets of the nephrolithiasis were searched from the database. The protein-protein interaction (PPI) network diagram and the drug-compounds-targets-disease network were constructed. The enrichment analysis was performed by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the effect of RP on the prevention and treatment of nephrolithiasis was experimentally validated in vivo. Animal experiments showed that RP ameliorates renal function and reduced crystal deposition in a mouse model. It may act through anti-inflammation and anti-apoptosis. Our study showed that RP could prevent and treat nephrolithiasis by inhibiting apoptosis and inflammation, which provided a new efficacy and clinical application for RP.

Is There a Two-Way Risk between Decreased Testosterone Levels and the Progression and Prognosis of Chronic Kidney Disease? A Cohort Study Based on the National Health and Nutrition Examination Survey Database.

PURPOSE: The causal relationship between the incidence and prognosis of chronic kidney disease (CKD) and serum testosterone levels in patients is not yet fully understood. This study aims to use the National Health and Nutrition Examination Survey (NHANES), a large-scale nationally representative sample, to investigate the relationship between CKD and testosterone. MATERIALS AND METHODS: This study included six NHANES cycles for linear regression analysis, verified by multiple imputation methods. Stratified analysis and subgroup analysis were used to demonstrate the stability of CKD's effect on testosterone. Furthermore, we used Kaplan-Meier plots and log-rank tests to evaluate differences in survival rates between CKD male patients with low and normal levels of testosterone. RESULTS: From a total of 71,163 subjects, the cohort selected 28,663 eligible participants. Results showed that CKD patients had testosterone levels 28.423 ng/mL (24.762, 32.083) lower than non-CKD patients. The results of multiple imputations (ß=27.700, 95% confidence interval: 23.427, 31.974) were consistent with those of linear regression analysis, and the numerical match was good. Stratified regression analysis, and subgroup analysis results showed that CKD had a significant impact on testosterone at different dimensions. Kaplan-Meier plots showed significantly reduced survival rates in low testosterone CKD male patients (p<0.0001). CONCLUSIONS: The results of this big data analysis suggest that there may be a two-way risk between low levels of testosterone and CKD. The testosterone levels of CKD patients were significantly lower than those of the non-CKD population, and CKD patients with low testosterone levels had poorer prognoses. These results suggest that correcting testosterone levels in a timely manner can have preventive and therapeutic effects on the progression of CKD.

IRE1α-XBP1 regulates PDK1-dependent induction of epithelial-mesenchymal transition in non-small cell lung cancer cells.

Mounting evidence indicates that activation of unfolded protein response (UPR) and metabolic reprogramming contribute to cancer cell migration and invasion, but the molecular mechanism of pro-EMT program through a coordinated action of UPR with metabolism has not been defined. In this study, we utilized ER stress-inducing reagent, thapsigargin (TG), to induced pharmacologic ER stress in lung cancer cells. Here. We report that the branch of UPR, IRE1α-XBP1 pathway plays a pivotal role in reprogramming lung cancer cell metabolism. At the molecular level, the expression of pyruvate dehydrogenase kinase-1 (PDK-1) is directly induced by XBP1 as a consequence of UPR activation, thus facilitating aerobic glycolysis and lactate production. We also demonstrated that PDK1 serves as a downstream element of UPR activation in induction of Snail and EMT program. In addition, PDK1-induced Snail was dependent on the lactate production derived from metabolic reprogramming. Our findings reveal a critical role of lactate in pro-invasion events and establishes a direct connection between ER-stress and metabolic reprogramming in facilitating cancer cell progression.

Lactate-fueled oxidative metabolism drives DNA methyltransferase 1-mediated transcriptional co-activator with PDZ binding domain protein activation.

Activity of transcriptional co-activator with PDZ binding domain (TAZ) protein is strongly implicated in the pathogenesis of human cancer and is influenced by tumor metabolism. High levels of lactate concentration in the tumor microenvironment as a result of metabolic reprogramming are inversely correlated with patient overall survival. Herein, we investigated the role of lactate in the regulation of the activity of TAZ and showed that glycolysis-derived lactate efficiently increased TAZ expression and activity in lung cancer cells. We showed that the reactive oxygen species (ROS) generated by lactate-fueled oxidative phosphorylation (OXPHOS) in mitochondria activated AKT and thereby inhibited glycogen synthase kinase 3 beta/beta-transducin repeat-containing proteins (GSK-3ß/ß-TrCP)-mediated ubiquitination and degradation of DNA methyltransferase 1 (DNMT1). Upregulation of DNMT1 by lactate caused hypermethylation of TAZ negative regulator of the LATS2 gene promoter, leading to TAZ activation. Moreover, TAZ binds to the promoter of DNMT1 and is necessary for DNMT1 transcription. Our study showed a molecular mechanism of DNMT1 in linking tumor metabolic reprogramming to the Hippo-TAZ pathway and functional significance of the DNMT1-TAZ feedback loop in the migratory and invasive potential of lung cancer cells.